Vitamin D (mine)

vit D is a

prohormone

vitamin D is derived from

cholesterol

how we make it from scratch

is in every cell of the body

vit D can be synthesized from

sun exposure

insufficient sun exposure is why vit D

is essential vit D

vit D synthesis is activated by ____ in ____ and_______

enzymes

liver and kidneys 

what are the 2 main organs needed for synthesis of vit D in active form?

kidney and liver 

vit D deficiency can cause (general)

diseases

what form of vit D do we get from plant foods 

ergosterol 

ergosterol (previt D2) —> _____

ergocalciferol (D2)

In our bodies, we derive vit D from

cholesterol

cholesterol on skin cells becomes what?

7-dehydrocholesterol

7-dehydrocholesterol exposed to UV becomes

lumisterol (lost as skin cells sloughed off)

7-dehydrocholesterol exposed to UVB on skin becomes

previtamin D3 (precalciferol)

precalceferol (previt D3) exposed to UV becomes

tachysterol (lost as skin cells are sloughed off)

precalceferol (previt D3) when undergoes thermal isomerization becomes

cholecalciferol (D3)

is cholecalciferol the active form of VitD?

nope

what does the subscript 3 in D3 mean? D2?

3 represents what is produce by human/animal sources

2 means originates from plants

which form of vit D is from plant sources?

ergosterol (converts into ergocalciferol)

D2 vs D3 bioavailability 

D2 is almost equivalent to D3 

supplements tend to be D2

__% of vitamin D is absorbed

50%

where is rate of absorption the highest? & where is most absorption?

rate is highest in duodenum/jejunum BUT

most absorption occurs in distal SI

vitamin D is incorporated into___ & transported through____

chylomicron

lymphatic system & then blood

chylomicrons transport ___% of cholecalciferol in the blood

40%

some (60%) of vit D transport involves what?

vit D binding protein (DBP)

aka transcalciferin

what tissues take vit D from chylomicron transport

adipose, muscle & other tissues

where is storage higher & when

adipose; when more fat is present

who requires a higher intake of vit D & to maintain what

obese individuals

to maintain blood concentration (in comparison to normal wt individuals)

in contrast to dietary vit D, vit D synthesized by the skin (cholecalciferol) goes into blood how?

diffuses slowly

vitamin synthesized by the skin is picked up by the ______ in the blood 

hepatic DBP

DBP can transport the vitamin primarily to ___ (other tissues take as needed)

liver

plasma transport involves ____% bound to ____

60% ; DBP (transcalciferin)

VIT D METABOLISM 

what form of vit D diffuses into the blood?

cholecalciferol

Cholecalciferol diffuses from  skin into blood & is picked up by ____ for transport

vitamin-D binding protein (DBP) —> aka transcalciferin

Vitamin D/cholecalciferol travels through blood as part of ___ or bound to ___

chylomicron ; DBP (transcalciferin)

cholecalciferol is metabolized into what form in the liver?

25-OH D (calcidiol)

cholecalciferol —> 25-OH D (calcidiol) via what enzyme? coenzyme?

25 hydroxylase (NADPH)

cholecalciferol —> 25-OH D (calcidiol) occurs where in the cell?

mitochondria 

majority of 25-OH D (calcidiol) is secreted into __

blood

majority of 25-OH D (calcidiol) is transported by

DBP (transcalciferin)

half life of 25-OH D (calcidiol)

2-3wks

normal serum concentrations of 25-OH D (know this**)

30-40ng/mL (ng = nanogram= 9 decimal places)

very very little amount… yet around 15% is suboptimal 

From blood, 25-OH-D is taken up by (mostly ____) in response to increases in ______ concentration.

kidney

increase in parathyroid hormone (PTH)

In the kidney proximal tubules, 25-OH-D and DBP bind to a ____________ to form a complex.

cubulin-megalin membrane receptor

The complex is internalized through _______

endocytosis

once in the kidney, 25-OH-D can be converted into ___________ or ___________—

1,25OH2D (calcitriol) OR 24,25-(OH)2D 

what kidney enzyme will convert 25-OH-D into 1,25(OH)2D (calcitriol)?

1-alpha hydroxylase (NADPH dependent) 

1-alpha hydroxylase is also known as what names?

1-hydrolase

alpha-hydrolase 

Majority of 1-alpha hydroxylase is found in the ______with smaller amounts in ......

kidney ; bone, skin, intestine, etc

Renal production of 1,25-OH2 D is tightly regulated by what 2 hormones

PTH and fibroblast-like growth factor (FGF)

PTH ) is produced by

fibroblast-like growth factor (FGF) is produced by

parathyroid gland

bone cells 

when will 25-OH-D be converted into 1,25(OH)2D (calcitriol) by 1-a hydrolase?

when high PTH and low calcium 

1,25-(OH)2D (calcitriol) can be converted further into other molecules via what enzyme and into what when calcitriol is high?

24-hydrolase

making 1,24,25(OH)2D

1,25-(OH)2D (calcitriol) acted upon 24-hydrolase occurs in what tissue?

kidney

1,25-(OH)2D + 24-hydroxylase -> what eventual compound

calcitroic acid 

calcitroic acid can be used as a .....

secondary maker for assessment (excreted in urine) 

what is primary marker for assessment?

25(OH)D (calcidiol)

when would 25(OH)2D (calcidiol) be converted into 24,25(OH)2D instead of 1,25(OH)2D

When Calcitriol is high

how is 25-OH D —>  24,25-(OH)2D (enzyme?)

24-hydroxylase

24,25-(OH)2D can then ...

release to blood bound to DBP to be carried to various tissues

what is the major circulating form of vit D

25-OH Vitamin D

what is 25-OH vit D used for?

measured for assessment and deficiency determination (primary assessment measure)

active form of vit D

1,25(OH)2

1,25(OH)2 half life & normal range

2-6 hours

normal range of 20-40 pg/dL (12 decimal places)

why is 25(OH)D used for assessment vs 1,25(OH)D?

because 1,25(OH)D has shorter half life AND smaller adequate range (pico vs nanograms) so 25(OH)D is easier to measure and can be done in most labs

Vitamin D binding protein responsible for .....

transport

vitamin D binding protein is also known as ***

Transcalciferin

ACTIVATION, TRANSPORT, STORAGE

Activation of vit D occurs by what tissues.....

liver & kidneys

vit D is stored in

liver & fat tissue

increased activation of D is linked to .....

Ca inadequacy, metabolism, & homeostasis

excretion of D mainly via

bile

VIT D ROLES AND ACTIONS

genomic action of Vit D involved what form?

1,25(OH)2D

1,25(OH)2D goes where for genomic action?

travels to nucleus of its target tissue cells

In the nucleus, 1,25(OH)2D binds to a ____

protein receptor

the complex (1,25(OH)2D with protein receptor) bind to what?

binds directly to DNA

the complex (1,25(OH)2D with protein receptor) binding to DNA, causes what?

increase or decrease gene transcription

in gene expression, calcitriol binds to 

vitamin D receptor (VDR) 

vit D receptor (VDR)-calcitriol forms heterodimer how?

with retinoid X receptor

VDR and RXR form what?

vitamin D response element (VDRE)

vitamin D response element (VDRE) then proceeds to ____ & then ____

changes in gene transcription

changes in protein synthesis

Vit D plays a role in making

important calcium binding proteins

vit D influences 2 important calcium binding proteins how?

its nuclear response element (VDRE) in the transcription machinery

Vitamin D via its nuclear response element in the transcription machinery influences what 2 important Ca binding proteins

calbindin & calmodulin

calbindin vs calmodulin

calbindin is the INTESTINAL binding protein

calmodulin is the intercellular binding protein (within in all cells)

what does calbindin do? where found?

found: found in the intestinal brush border 

function: brings in calcium into the intestinal cell 

for calcium-binding action, what form of Vit D is used?

1,25(OH)2D (calcitriol)

how does vit D play a role in calbindin? (think illustration)

1,25(OH)2D goes into intestinal cell as will bind to VDR to form complex—> goes to nucleus to make calbindin mRNA which will then go to cytosol to ER and be made into calbindin 

calbindin made then does what?

goes to brush border and functions to allow calcium absorption in the intestine

how does calcium enter the intestinal cell?

via specialized channel and the transport of calbindin

calcium exits the intestinal cell via

active transport

non-genomic actions of 1,25(OH)2D involves

Intracellular signaling (signal transduction pathways)

what 3 things does vit D do through signal transduction pathways?

• increased calcium uptake

• increased intracellular concentration

• transcellular calcium flux in enterocytes, osteoblasts, adipocytes, and skeletal muscle.

Primary function of active D (1,25(OH)2D

maintain an optimal serum Ca level (8.5-10.5mg/dL)

how does active D maintain optimal serum Ca level (3 things)

-Increasing Ca absorption from intestine

-Increasing Ca reabsorption from kidney

-Increasing Ca resorption from bone

1,25(OH)2D functions in what tissues for calcium levels (3)

intestine, kidney, bone

intestine, kidney, bone contribute to ....

plasma Ca++

plasma Ca++ contributes to

mineralization & neuromuscular function

1,25(OH)2D is ____

extremely potent